The scaffolding function of LSD1 controls DNA methylation in mouse ESCs.

ABSTRACT: Lysine-specific histone demethylase 1 (LSD1), which demethylates mono- or di- methylated histone H3 on lysine 4 (H3K4me1/2), is essential for early embryogenesis and development. Here we show that LSD1 is dispensable for mouse embryonic stem cell (ESC) self-renewal but is required for mouse ESC growth and differentiation. Reintroduction of a catalytically-impaired LSD1 (LSD1^MUT) recovers the proliferation capability of mouse ESCs, yet the enzymatic activity of LSD1 is essential to ensure proper differentiation. Indeed, increased H3K4me1 in Lsd1 knockout (KO) mouse ESCs does not lead to major changes in global gene expression programs related to stemness. However, ablation of LSD1 but not LSD1^MUT results in decreased DNMT1 and UHRF1 proteins coupled to global hypomethy

SUBMITTER: Malla S 

PROVIDER: S-EPMC11377572 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature